DESCRIPTION The proposed project addresses the ability of competitive N-methyl-D-aspartate (NMDA) receptor antagonists to affect responding conditioned with drugs of abuse (morphine, cocaine). It is proposed to study in rats the influence of site-selective NMDA antagonists on: (1) the drug-conditioned activation of locomotor activity; (2) the facilitation of intracranial self-stimulation induced by conditioned stimuli associated with abused drugs or rewarding electrical stimulation; (3) the responding maintained by conditioned reinforcers using intravenous drug self-administration procedures. The NMDA antagonists are to be administered systemically and also centrally into the nucleus accumbens septi through chronically implanted cannuli. The results will clarify the role of the glutamatergic excitatory system, especially its projections to the nucleus accumbens, in mediating the expression of responses conditioned through exposure to drugs of abuse. Secondarily, considering the role conditioned drug effects may have for relapse to, and maintenance of, drug seeking, the results may also provide important directions for the development of medications for the treatment of drug abuse.